ArticleMolecular biology of the cell2000
Caspase-mediated cleavage of p130cas in etoposide-induced apoptotic Rat-1 cells.
Article in Molecular biology of the cell, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 73 citations in OpenAlex.
- Anoikis: To Die or Not to Die?International journal of molecular sciences · 2026Review
- The p130Cas-Crk/CrkL Axis: A Therapeutic Target for Invasive Cancers Unveiled by Collaboration Among p130Cas, Crk, and CrkL.International journal of molecular sciences · 2025Review
- Identification of a novel type of focal adhesion remodelling via FAK/FRNK replacement, and its contribution to cancer progression.Cell death & disease · 2023Article
- p130Cas is required for androgen-dependent postnatal development regulation of submandibular glands.Scientific reports · 2023Article
- Endothelial p130cas confers resistance to anti-angiogenesis therapy.Cell reports · 2022Article
- Structural and functional analysis of cell adhesion and nuclear envelope nano-topography in cell death.Scientific reports · 2015Article
- Apoptotic cell clearance: basic biology and therapeutic potential.Nature reviews. Immunology · 2014Review
- Silencing of p130cas in ovarian carcinoma: a novel mechanism for tumor cell death.Journal of the National Cancer Institute · 2011Article
- Article
- Integrin αβ1, αvβ, α6β effectors p130Cas, Src and talin regulate carcinoma invasion and chemoresistance.Biochemical and biophysical research communications · 2011Article
- MCL-1 is a stress sensor that regulates autophagy in a developmentally regulated manner.The EMBO journal · 2011Article
- P130Cas attenuates epidermal growth factor (EGF) receptor internalization by modulating EGF-triggered dynamin phosphorylation.PloS one · 2011Article
- Article
- The SH2 domain protein Shep1 regulates the in vivo signaling function of the scaffolding protein Cas.Cellular signalling · 2010Article
- CAS proteins in normal and pathological cell growth control.Cellular and molecular life sciences : CMLS · 2010Review
- The Leishmania surface protease GP63 cleaves multiple intracellular proteins and actively participates in p38 mitogen-activated protein kinase inactivation.The Journal of biological chemistry · 2009Article
- A novel association between p130Cas and resistance to the chemotherapeutic drug adriamycin in human breast cancer cells.Cancer research · 2008Article
- The integrin-coupled signaling adaptor p130Cas suppresses Smad3 function in transforming growth factor-beta signaling.Molecular biology of the cell · 2008Article
- Caspase-3 regulates catalytic activity and scaffolding functions of the protein tyrosine phosphatase PEST, a novel modulator of the apoptotic response.Molecular and cellular biology · 2007Article
- Molecular basis for HEF1/NEDD9/Cas-L action as a multifunctional co-ordinator of invasion, apoptosis and cell cycle.Cell biochemistry and biophysics · 2007Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Apoptosis causes characteristic morphological changes in cells, including membrane blebbing, cell detachment from the extracellular matrix, and loss of cell-cell contacts. We investigated the changes in focal adhesion proteins during etoposide-induced apoptosis in Rat-1 cells and found that during apoptosis, p130cas (Crk-associated substrate [Cas]) is cleaved by caspase-3. Sequence analysis showed that Cas contains 10 DXXD consensus sites preferred by caspase-3. We identified two of these sites (DVPD(416)G and DSPD(748)G) in vitro, and point mutations substituting the Asp of DVPD(416)G and DSPD(748)G with Glu blocked caspase-3-mediated cleavage. Cleavage at DVPD(416)G generated a 74-kDa fragment, which was in turn cleaved at DSPD(748)G, yielding 47- and 31-kDa fragments. Immunofluorescence microscopy revealed well-developed focal adhesion sites in control cells that dramatically declined in number in etoposide-treated cells. Cas cleavage correlated temporally with the onset of apoptosis and coincided with the loss of p125FAK (focal adhesion kinase [FAK]) from focal adhesion sites and the attenuation of Cas-paxillin interactions. Considering that Cas associates with FAK, paxillin, and other molecules involved in the integrin signaling pathway, these results suggest that caspase-mediated cleavage of Cas contributes to the disassembly of focal adhesion complexes and interrupts survival signals from the extracellular matrix.
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